dnc-1/dynactin 1 Knockdown Disrupts Transport of Autophagosomes and Induces Motor Neuron Degeneration

• DOI: 10.1371/journal.pone.0054511
• Publication Date: 2013-02-07T22:15:42Z
• Authors: Kensuke Ikenaka; Kaori Kawai; Masahisa Katsuno; Zhe Huang; Yue-Mei Jiang; Yohei Iguchi; Kyogo Kobayashi; Tsubasa Kimata; Masahiro Waza; Fumiaki Tanaka; Ikue Mori; Gen Sobue
• Keywords: Dynactin; Axoplasmic transport

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. We previously showed that expression dynactin 1, an axon protein regulating retrograde transport, markedly reduced in spinal neurons sporadic ALS patients, although mechanisms which decreased 1 levels cause neurodegeneration have yet to be elucidated. The accumulation autophagosomes degenerated another key pathological feature ALS. Since are cargo dynein/dynactin complexes and play crucial role turnover several organelles proteins, we hypothesized quantitative disrupts transport induces degeneration neuron. In present study, generated Caenorhabditis elegans model DNC-1, homolog specifically knocked down This exhibited severe defects together with axonal neuronal degeneration. also observed impaired movement increased number Furthermore, combination rapamycin, activator autophagy, trichostatin facilitates dramatically ameliorated phenotype this model. Thus, our results suggest neuron novel substantial therapeutic target for